1994 Fiscal Year Final Research Report Summary
Effects of Ascorbic Acid on the Metabolic Fate and the Hepatitis of Hydrazine Derivatives
| Project/Area Number |
05671899
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | University of Tokushima |
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Principal Investigator |
MATSUKI Yoko University of Tokushima, Fac.of Pharmaceutical Sci., 薬学部, 助手 (20035546)
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| Co-Investigator(Kenkyū-buntansha) |
KIWADA Hiroshi University of Tokushima, Fac.of Pharmaceutical Sci., 薬学部, 教授 (50120184)
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| Project Period (FY) |
1993 – 1994
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| Keywords | ascorbic acid / metabolic fate / hydradine derivatives / free radical / hepatitis / hepatic function / radical scavenger / aminophrine clearance |
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| Research Abstract |
In the excretion of iproniazid (IPN) and its metabolites except hydrazine (Hy), the differences between co-administration and single administration was not observed. Furthermore, AA did not affect both absorption and metabolism of IPN.
In the presence of AA,the free radical formations of Hy, isoniazid (INAH) and acetylhydradine were significantly inhibited by the use of ESR spectroscopy and of spin-trapping technique. The free radical formations of IPN and isopropylhydrazine (IP-Hy), intermediate of IPN,were also significantly inhibited by AA in a dose dependent manner.
In vivo experiments, the radical generations after i.p.administraion of IPN with AA were significantly depressed in plasma and liver, compared with those after the administration of IPN alone. Based on these results, it was suggested that AA may reduce the INAH and IPN and IPN induced hepatitis.
The 4-POBN-trapped radical species generatated from IPN and IP-Hy were identified as isopropyl radical and the radical species from Hy was Hy radical by the results of mass spectrometry.
The effects of ascorbic acid (AA) on hepatic injury induced by IPN investigated by the evaluation of hepatic function using the clearance of aminopyrine (AM). Pretreatment with IPN with AA led to a marked increase in the k_<el> and in the clearance of AM compared with pretreatment using IPN alone. A significant increase in the k_<el> and the clearance of AM was also found in the case of combined pretreatment using IP-Hy with AA.
The effects of AA on the hepatic injury induced by IPN were studied according to its histological aspects. In the specimens obtained following the administration of IPN or IP-Hy with AA,the degree of cell necrosis was remarkably lowed both quantitatively and qualitatively.
The present results clearly demonstrate that AA was effective in reducing IPN-induced hepatitis.
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